Spinal Muscular Atrophy (SMA) is a progressive neuromuscular disease associated with typically proximal muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord.1
With the widespread use of genetic techniques to diagnose SMA, clinicians now rarely use pathology specimens to confirm SMA diagnosis.2,3 A current diagnostic algorithm proposed by a consensus panel of SMA experts does not mention muscle biopsy.4 Muscle MRI is emerging as an alternative, non-invasive, modality to evaluate muscle pathology in patients with SMA.5
Biopsy specimens from an affected muscle in a patient with SMA will feature neurogenic changes owing to the loss of nervous innervation to the muscles.1 Investigators have published a description of a myopathic-like pathology in SMN1-negative cases of SMA.6
At the gross level, atrophy and fatty infiltration can be visible in biopsied muscle from patients with SMA.7
At the microscopic level, there is the classically described appearance of bundles or sheets of atrophic fibers mixed amongst normal or large appearing fibers.7,8 Type I muscle fibers can be rounded shape, may be atrophic or even normal in diameter;9 sometimes type I fibers can appear enlarged because of adjacent fibers being so atrophic.10 Type II muscle fiber pathology is more predictable; there is typically some hypertrophy of type II muscle fibers present even in severely affected infantile onset cases.7,10 In SMA types 3 and 4, muscle pathology reveals a more uniform appearance of atrophic fiber bundles nested amongst normal diameter healthy appearing fibers.3 In later onset SMAs, non-atrophic fibers will reside within abnormally large bundles, and typically all fibers within these groupings will be of a single kind, usually type I.3
At the ultrastructural level, the relative distribution of type I and II fibers is variable, but there is almost always reduced cytoplasm, disordered contractile elements, and empty sleeves of basal lamina.11
The severity of muscle pathology does not correlate with the clinical extent of SMA,11 and variability in findings means that even well described pathology cannot distinguish one type of SMA from another.3
1. Prior TW, Finanger E. Spinal Muscular Atrophy. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews((R)). Seattle (WA): University of Washington, Seattle University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.
2. Harding BN, Kariya S, Monani UR, et al. Spectrum of neuropathophysiology in spinal muscular atrophy type I. J Neuropathol Exp Neurol. 2015;74(1):15-24.
3. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015;51(2):157-167.
4. Glascock J, Sampson J, Haidet-Phillips A, et al. Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening. J Neuromuscul Dis. 2018;5(2):145-158.
5. Liu GC, Jong YJ, Chiang CH, Yang CW. Spinal muscular atrophy: MR evaluation. Pediatric radiology. 1992;22(8):584-586.
6. Rossor AM, Oates EC, Salter HK, et al. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015;138(Pt 2):293-310.
7. Hsu CF, Chen CY, Yuh YS, Chen YH, Hsu YT, Zimmerman RA. MR findings of Werdnig-Hoffmann disease in two infants. AJNR American journal of neuroradiology. 1998;19(3):550-552.
8. Fenichel GM, Engel WK. HISTOCHEMISTRY OF MUSCLE IN INFANTILE SPINAL MUSCULAR ATROPHY. Neurology. 1963;13:1059-1066.
9. Omran H, Ketelsen UP, Heinen F, et al. Axonal neuropathy and predominance of type II myofibers in infantile spinal muscular atrophy. J Child Neurol. 1998;13(7):327-331.
10. Kingma DW, Feeback DL, Marks WA, Bobele GB, Leech RW, Brumback RA. Selective type II muscle fiber hypertrophy in severe infantile spinal muscular atrophy. J Child Neurol. 1991;6(4):329-334.
11. Zalneraitis EL, Halperin JJ, Grunnet ML, Russman BS, Peress N. Muscle biopsy and the clinical course of infantile spinal muscular atrophy. J Child Neurol. 1991;6(4):324-328.